Construct Cohort Inclusion and Restriction Criteria Expressions

Wraps the 'CIRCE' (< https://github.com/ohdsi/circe-be>) 'Java' library allowing cohort definition expressions to be edited and converted to 'Markdown' or 'SQL'.

Quantile Binned Plots

Create quantile binned and conditional plots for Exploratory Data Analysis. The package provides several plotting functions that are all based on quantile binning. The plots are created with 'ggplot2' and 'patchwork' and can be further adjusted.

Create and Explore Geographic Zoning Systems

Functions, documentation and example data to help divide geographic space into discrete polygons (zones). The package supports new zoning systems that are documented in the accompanying paper, "ClockBoard: A zoning system for urban analysis", by Lovelace et al. (2022) . The functions are motivated by research into the merits of different zoning systems (Openshaw, 1977) . A flexible ClockBoard zoning system is provided, which breaks-up space by concentric rings and radial lines emanating from a central point. By default, the diameter of the rings grow according to the triangular number sequence (Ross & Knott, 2019) with the first 4 doughnuts (or annuli) measuring 1, 3, 6, and 10 km wide. These annuli are subdivided into equal segments (12 by default), creating the visual impression of a dartboard. Zones are labelled according to distance to the centre and angular distance from North, creating a simple geographic zoning and labelling system useful for visualising geographic phenomena with a clearly demarcated central location such as cities.

Interpreting Time Series and Autocorrelated Data Using GAMMs

GAMM (Generalized Additive Mixed Modeling; Lin & Zhang, 1999) as implemented in the R package 'mgcv' (Wood, S.N., 2006; 2011) is a nonlinear regression analysis which is particularly useful for time course data such as EEG, pupil dilation, gaze data (eye tracking), and articulography recordings, but also for behavioral data such as reaction times and response data. As time course measures are sensitive to autocorrelation problems, GAMMs implements methods to reduce the autocorrelation problems. This package includes functions for the evaluation of GAMM models (e.g., model comparisons, determining regions of significance, inspection of autocorrelational structure in residuals) and interpreting of GAMMs (e.g., visualization of complex interactions, and contrasts).

Standard Dataset Manager for Observational Medical Outcomes Partnership Common Data Model Sample Datasets

Facilitates access to sample datasets from the 'EunomiaDatasets' repository (< https://github.com/ohdsi/EunomiaDatasets>).

Data and Statistical Analyses after Multiple Imputation

Statistical Analyses and Pooling after Multiple Imputation. A large variety of repeated statistical analysis can be performed and finally pooled. Statistical analysis that are available are, among others, Levene's test, Odds and Risk Ratios, One sample proportions, difference between proportions and linear and logistic regression models. Functions can also be used in combination with the Pipe operator. More and more statistical analyses and pooling functions will be added over time. Heymans (2007) . Eekhout (2017) . Wiel (2009) . Marshall (2009) . Sidi (2021) . Lott (2018) . Grund (2021) .

Prediction Model Pooling, Selection and Performance Evaluation Across Multiply Imputed Datasets

Pooling, backward and forward selection of linear, logistic and Cox regression models in multiply imputed datasets. Backward and forward selection can be done from the pooled model using Rubin's Rules (RR), the D1, D2, D3, D4 and the median p-values method. This is also possible for Mixed models. The models can contain continuous, dichotomous, categorical and restricted cubic spline predictors and interaction terms between all these type of predictors. The stability of the models can be evaluated using (cluster) bootstrapping. The package further contains functions to pool model performance measures as ROC/AUC, Reclassification, R-squared, scaled Brier score, H&L test and calibration plots for logistic regression models. Internal validation can be done across multiply imputed datasets with cross-validation or bootstrapping. The adjusted intercept after shrinkage of pooled regression coefficients can be obtained. Backward and forward selection as part of internal validation is possible. A function to externally validate logistic prediction models in multiple imputed datasets is available and a function to compare models. For Cox models a strata variable can be included. Eekhout (2017) . Wiel (2009) . Marshall (2009) .

Parentage Assignment using Bi-Allelic Genetic Markers

Can be used for paternity and maternity assignment and outperforms conventional methods where closely related individuals occur in the pool of possible parents. The method compares the genotypes of offspring with any combination of potentials parents and scores the number of mismatches of these individuals at bi-allelic genetic markers (e.g. Single Nucleotide Polymorphisms). It elaborates on a prior exclusion method based on the Homozygous Opposite Test (HOT; Huisman 2017 ) by introducing the additional exclusion criterion HIPHOP (Homozygous Identical Parents, Heterozygous Offspring are Precluded; Cockburn et al., in revision). Potential parents are excluded if they have more mismatches than can be expected due to genotyping error and mutation, and thereby one can identify the true genetic parents and detect situations where one (or both) of the true parents is not sampled. Package 'hiphop' can deal with (a) the case where there is contextual information about parentage of the mother (i.e. a female has been seen to be involved in reproductive tasks such as nest building), but paternity is unknown (e.g. due to promiscuity), (b) where both parents need to be assigned, because there is no contextual information on which female laid eggs and which male fertilized them (e.g. polygynandrous mating system where multiple females and males deposit young in a common nest, or organisms with external fertilisation that breed in aggregations). For details: Cockburn, A., Penalba, J.V.,Jaccoud, D.,Kilian, A., Brouwer, L., Double, M.C., Margraf, N., Osmond, H.L., van de Pol, M. and Kruuk, L.E.B. (in revision). HIPHOP: improved paternity assignment among close relatives using a simple exclusion method for bi-allelic markers. Molecular Ecology Resources, DOI to be added upon acceptance.

Routines for Performing Empirical Calibration of Observational Study Estimates

Routines for performing empirical calibration of observational study estimates. By using a set of negative control hypotheses we can estimate the empirical null distribution of a particular observational study setup. This empirical null distribution can be used to compute a calibrated p-value, which reflects the probability of observing an estimated effect size when the null hypothesis is true taking both random and systematic error into account. A similar approach can be used to calibrate confidence intervals, using both negative and positive controls. For more details, see Schuemie et al. (2013) and Schuemie et al. (2018) .

Synthesizing Causal Evidence in a Distributed Research Network

Routines for combining causal effect estimates and study diagnostics across multiple data sites in a distributed study, without sharing patient-level data. Allows for normal and non-normal approximations of the data-site likelihood of the effect parameter.