Dataset Information

ICARE: An R package to build, validate and apply absolute risk models.

ABSTRACT: This report describes an R package, called the Individualized Coherent Absolute Risk Estimator (iCARE) tool, that allows researchers to build and evaluate models for absolute risk and apply them to estimate an individual's risk of developing disease during a specified time interval based on a set of user defined input parameters. An attractive feature of the software is that it gives users flexibility to update models rapidly based on new knowledge on risk factors and tailor models to different populations by specifying three input arguments: a model for relative risk, an age-specific disease incidence rate and the distribution of risk factors for the population of interest. The tool can handle missing information on risk factors for individuals for whom risks are to be predicted using a coherent approach where all estimates are derived from a single model after appropriate model averaging. The software allows single nucleotide polymorphisms (SNPs) to be incorporated into the model using published odds ratios and allele frequencies. The validation component of the software implements the methods for evaluation of model calibration, discrimination and risk-stratification based on independent validation datasets. We provide an illustration of the utility of iCARE for building, validating and applying absolute risk models using breast cancer as an example.

SUBMITTER: Pal Choudhury P

PROVIDER: S-EPMC7001949 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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iCARE: An R package to build, validate and apply absolute risk models.

Pal Choudhury Parichoy P Maas Paige P Wilcox Amber A Wheeler William W Brook Mark M Check David D Garcia-Closas Montserrat M Chatterjee Nilanjan N

PloS one 20200205 2

This report describes an R package, called the Individualized Coherent Absolute Risk Estimator (iCARE) tool, that allows researchers to build and evaluate models for absolute risk and apply them to estimate an individual's risk of developing disease during a specified time interval based on a set of user defined input parameters. An attractive feature of the software is that it gives users flexibility to update models rapidly based on new knowledge on risk factors and tailor models to different ...[more]

PMID: 32023287

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Project description:BACKGROUND:There has been increasing interest in assessing the impacts of extreme temperatures on mortality due to diseases of the circulatory system. This is further relevant for future climate scenarios where marked changes in climate are expected. This paper presents a solid method do identify the relationship between extreme temperatures and mortality risk by using as predictors simulated temperature data for cold and hot conditions in two urban areas in Portugal. METHODS:Based on the mortality and meteorological data from Porto Metropolitan Area (PMA) and Lisbon Metropolitan Area (LMA), a distributed lag nonlinear model (DLNM) was implemented to estimate the temperature effects on mortality due to diseases of the circulatory system. The performance of the models was validated via bootstrapping approaching by creating resamples with replacement from the validating data. Bootstrapping was also used to identify the best candidate model and to evaluate the sensitivity of the spline functions to the exposure-lag-response relationship. RESULTS:It is found that the model is able to reproduce the temperature-related mortality risk for two metropolitan areas. Temperature previously simulated by climate models is useful and even better than observed temperature. Although, the biases in predictions in both metropolitan areas are low, mortality risk predictions in PMA are more accurate than in LMA. Using parametric bootstrapping, we found that the overall cumulative association estimated under different bi-dimensional exposure-lag-response relationship are relatively stable, especially for the model selected by Quasi-Akaike Information Criteria (QAIC). Exposure to summer temperature conditions is best related to mortality risk. The association between winter temperature and mortality risk is somewhat less strong. CONCLUSIONS:The use of QAIC to choose from several candidate models provides valid predictions and reduced the uncertainty in the estimated relative risk for circulatory disease mortality. Our findings can be applied to better understand the characteristics and facilitate the prevention of circulatory disease mortality in Porto and Lisbon Metropolitan Areas, namely if we consider the actual context of climate change.

Project description:There is an increasing need in biology and clinical medicine to robustly and reliably measure tens to hundreds of peptides and proteins in clinical and biological samples with high sensitivity, specificity, reproducibility, and repeatability. Previously, we demonstrated that LC-MRM-MS with isotope dilution has suitable performance for quantitative measurements of small numbers of relatively abundant proteins in human plasma and that the resulting assays can be transferred across laboratories while maintaining high reproducibility and quantitative precision. Here, we significantly extend that earlier work, demonstrating that 11 laboratories using 14 LC-MS systems can develop, determine analytical figures of merit, and apply highly multiplexed MRM-MS assays targeting 125 peptides derived from 27 cancer-relevant proteins and seven control proteins to precisely and reproducibly measure the analytes in human plasma. To ensure consistent generation of high quality data, we incorporated a system suitability protocol (SSP) into our experimental design. The SSP enabled real-time monitoring of LC-MRM-MS performance during assay development and implementation, facilitating early detection and correction of chromatographic and instrumental problems. Low to subnanogram/ml sensitivity for proteins in plasma was achieved by one-step immunoaffinity depletion of 14 abundant plasma proteins prior to analysis. Median intra- and interlaboratory reproducibility was <20%, sufficient for most biological studies and candidate protein biomarker verification. Digestion recovery of peptides was assessed and quantitative accuracy improved using heavy-isotope-labeled versions of the proteins as internal standards. Using the highly multiplexed assay, participating laboratories were able to precisely and reproducibly determine the levels of a series of analytes in blinded samples used to simulate an interlaboratory clinical study of patient samples. Our study further establishes that LC-MRM-MS using stable isotope dilution, with appropriate attention to analytical validation and appropriate quality control measures, enables sensitive, specific, reproducible, and quantitative measurements of proteins and peptides in complex biological matrices such as plasma.

Dataset Information

ICARE: An R package to build, validate and apply absolute risk models.

Publications

iCARE: An R package to build, validate and apply absolute risk models.

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