These guidelines are meant to provide a pragmatic, yet rigorous, help to drug developers and decision makers, since they are shaped by three fundamental ingredients: the clinically determined margin of detriment on OS that is unacceptably high (delta null); the benefit on OS that is plausible given the mechanism of action of the novel intervention (delta alt); and the quantity of information (i.e. survival events) it is feasible to accrue given the clinical and drug development setting. The proposed guidelines facilitate transparent discussions between stakeholders focusing on the risks of erroneous decisions and what might be an acceptable trade-off between power and the false positive error rate.

This package contains functions that allow Bayesian meta-analysis (1) with binomial data, counts(y) and total counts (n) or, (2) with user-supplied point estimates and associated variances. Case (1) provides an analysis based on the logit transformation of the sample proportion. This methodology is also appropriate for combining data from sample surveys and related sources. The functions can calculate the corresponding similarity matrix. More details can be found in Cahoy and Sedransk (2023), Cahoy and Sedransk (2022) <doi:10.1007/s42519-018-0027-2>, Evans and Sedransk (2001) <doi:10.1093/biomet/88.3.643>, and Malec and Sedransk (1992) <doi:10.1093/biomet/79.3.593>.

Fit a logistic regression model using Firth's bias reduction method, equivalent to penalization of the log-likelihood by the Jeffreys prior. Confidence intervals for regression coefficients can be computed by penalized profile likelihood. Firth's method was proposed as ideal solution to the problem of separation in logistic regression, see Heinze and Schemper (2002) <doi:10.1002/sim.1047>. If needed, the bias reduction can be turned off such that ordinary maximum likelihood logistic regression is obtained. Two new modifications of Firth's method, FLIC and FLAC, lead to unbiased predictions and are now available in the package as well, see Puhr et al (2017) <doi:10.1002/sim.7273>.

Classification of pediatric tumors into biologically defined subtypes is challenging and multifaceted approaches are needed. For this aim, we developed a diagnostic classifier based on DNA methylation profiles. We offer MethPed as an easy-to-use toolbox that allows researchers and clinical diagnosticians to test single samples as well as large cohorts for subclass prediction of pediatric brain tumors. The current version of MethPed can classify the following tumor diagnoses/subgroups: Diffuse Intrinsic Pontine Glioma (DIPG), Ependymoma, Embryonal tumors with multilayered rosettes (ETMR), Glioblastoma (GBM), Medulloblastoma (MB) - Group 3 (MB_Gr3), Group 4 (MB_Gr3), Group WNT (MB_WNT), Group SHH (MB_SHH) and Pilocytic Astrocytoma (PiloAstro).

An automated and streamlined workflow for predictive climate mapping using climate station data. Works within an environment the user provides a destined path to - otherwise it's tempdir(). Quick and relatively easy creation of resilient and reproducible climate models, predictions and climate maps, shortening the usually long and complicated work of predictive modelling. For more information, please find the provided URL. Many methods in this package are new, but the main method is based on a workflow from Meyer (2019) <doi:10.1016/j.ecolmodel.2019.108815> and Meyer (2022) <doi:10.1038/s41467-022-29838-9> , however, it was generalized and adjusted in the context of this package.

Three sets of data and functions for informing ecosystem restoration decisions, particularly in the context of the U.S. Army Corps of Engineers. First, model parameters are compiled as a data set and associated metadata for over 300 habitat suitability models developed by the U.S. Fish and Wildlife Service (USFWS 1980, <https://www.fws.gov/policy-library/870fw1>). Second, functions for conducting habitat suitability analyses both for the models described above as well as generic user-specified model parameterizations. Third, a suite of decision support tools for conducting cost-effectiveness and incremental cost analyses (Robinson et al. 1995, IWR Report 95-R-1, U.S. Army Corps of Engineers).

An R-based application for exploratory data analysis of global EvapoTranspiration (ET) datasets. evapoRe enables users to download, validate, visualize, and analyze multi-source ET data across various spatio-temporal scales. Also, the package offers calculation methods for estimating potential ET (PET), including temperature-based, combined type, and radiation-based approaches described in : Oudin et al., (2005) <doi:10.1016/j.jhydrol.2004.08.026>. evapoRe supports hydrological modeling, climate studies, agricultural research, and other data-driven fields by facilitating access to ET data and offering powerful analysis capabilities. Users can seamlessly integrate the package into their research applications and explore diverse ET data at different resolutions.

This package provides a long-term forecast model called "Jubilee-Tectonic model" is implemented to forecast future returns of the U.S. stock market, Treasury yield, and gold price. The five-factor model forecasts the 10-year and 20-year future equity returns with high R-squared above 80 percent. It is based on linear growth and mean reversion characteristics in the U.S. stock market. This model also enhances the CAPE model by introducing the hypothesis that there are fault lines in the historical CAPE, which can be calibrated and corrected through statistical learning. In addition, it contains a module for business cycles, optimal interest rate, and recession forecasts.

This package creates interactive trees that can be included in Shiny apps and R markdown documents. A tree allows to represent hierarchical data (e.g. the contents of a directory). Similar to the shinyTree package but offers more features and options, such as the grid extension, restricting the drag-and-drop behavior, and settings for the search functionality. It is possible to attach some data to the nodes of a tree and then to get these data in Shiny when a node is selected. Also provides a Shiny gadget allowing to manipulate one or more folders, and a Shiny module allowing to navigate in the server side file system.

Obtain least-squares means for linear, generalized linear, and mixed models. Compute contrasts or linear functions of least-squares means, and comparisons of slopes. Plots and compact letter displays. Least-squares means were proposed in Harvey, W (1960) "Least-squares analysis of data with unequal subclass numbers", Tech Report ARS-20-8, USDA National Agricultural Library, and discussed further in Searle, Speed, and Milliken (1980) "Population marginal means in the linear model: An alternative to least squares means", The American Statistician 34(4), 216-221 <doi:10.1080/00031305.1980.10483031>. NOTE: lsmeans now relies primarily on code in the emmeans package. lsmeans will be archived in the near future.

Estimates propensity scores by the outcome-adaptive lasso of Shortreed and Ertefaie (2017) <doi:10.1111/biom.12679> and the generalized outcome-adaptive lasso (GOAL) of Balde, Yang and Lefebvre (2023) <doi:10.1111/biom.13683>, using glmnet with an exact penalty-scale correction so that the published objectives and tuning grids are reproduced. Tuning is by the weighted absolute mean difference balance criterion. The resulting score is designed to be supplied directly to the matchit() function of MatchIt as a distance measure, to the weightit() function of WeightIt as a propensity score, or to the psave() function of psAve as an appended candidate.

The main function, plot_GMM, is used for plotting output from Gaussian mixture models (GMMs), including both densities and overlaying mixture weight component curves from the fit GMM. The package also include the function, plot_cut_point, which plots the cutpoint (mu) from the GMM over a histogram of the distribution with several color options. Finally, the package includes the function, plot_mix_comps, which is used in the plot_GMM function, and can be used to create a custom plot for overlaying mixture component curves from GMMs. For the plot_mix_comps function, usage most often will be specifying the "fun" argument within "stat_function" in a ggplot2 object.

Facilitates population-level analysis of ligand-receptor (LR) interactions using large-scale single-cell transcriptomic data. Identifies significant LR pairs and quantifies their interactions through correlation-based filtering and projection score computations. Designed for large-sample single-cell studies, the package employs statistical modeling, including linear regression, to investigate LR relationships between cell types. It provides a systematic framework for understanding cell-cell communication, uncovering regulatory interactions and signaling mechanisms. Offers tools for LR pair-level, sample-level, and differential interaction analyses, with comprehensive visualization support to aid biological interpretation. The methodology is described in a manuscript currently under review and will be referenced here once published or publicly available.

Identifying cell types based on expression profiles is a pillar of single cell analysis. scROSHI identifies cell types based on expression profiles of single cell analysis by utilizing previously obtained cell type specific gene sets. It takes into account the hierarchical nature of cell type relationship and does not require training or annotated data. A detailed description of the method can be found at: Michael Prummer, Anne Bertolini, Lars Bosshard, Florian Barkmann, Josephine Yates, Valentina Boeva, The Tumor Profiler Consortium , Daniel Stekhoven, Franziska Singer, scROSHI: robust supervised hierarchical identification of single cells, NAR Genomics and Bioinformatics, Volume 5, Issue 2, June 2023, lqad058, <doi:10.1093/nargab/lqad058>.

Stress Response score (SRscore) is a stress responsiveness measure for transcriptome datasets and is based on the vote-counting method. The SRscore is determined to evaluate and score genes on the basis of the consistency of the direction of their regulation (Up-regulation, Down-regulation, or No change) under stress conditions across multiple analyzed research projects. This package is based on the HN-score (score based on the ratio of gene expression between hypoxic and normoxic conditions) proposed by Tamura and Bono (2022) <doi:10.3390/life12071079>, and can calculate both the original method and an extended calculation method described in Fukuda et al. (2025) <doi:10.1093/plphys/kiaf105>.

Computation of stopping boundaries for a single-arm trial using a Bayesian criterion. For each m<=n (n=total patient number of the trial) the smallest number of observed toxicities is calculated leading to the termination of the trial/accrual according to the specified criteria. The probabilities of stopping the trial/accrual at and up until (resp.) the m-th patient (m<=n) is also calculated. This design is more conservative than the frequentist approach (using Clopper Pearson CIs) which might be preferred as it concerns safety. See also Aamot et al. (2010) "Continuous monitoring of toxicity in clinical Trials - simulating the risk of stopping prematurely" <doi:10.5414/cpp48476>.

Density, distribution function, quantile function, and random generation function, maximum likelihood estimation (MLE), penalized maximum likelihood estimation (PMLE), the quartiles method estimation (QM), and median rank estimation (MEDRANK) for the two-parameter exponential distribution. MLE and PMLE are based on Mengjie Zheng (2013)<https://scse.d.umn.edu/sites/scse.d.umn.edu/files/mengjie-thesis_masters-1.pdf>. QM is based on Entisar Elgmati and Nadia Gregni (2016)<doi:10.5539/ijsp.v5n5p12>. MEDRANK is based on Matthew Reid (2022)<doi:10.5281/ZENODO.3938000>. In addition, the functions for computing the Kolmogorov-Smirnov (D) statistic, the Cramér-von Mises statistic, and the Andersonâ Darling statistic are provided.

Fits variance-guided linear regression models that provide an alternative to ordinary least squares (OLS) for general linear-model design matrices, including ANOVA-style encodings. The methods use an iteratively reweighted least squares estimator or an iteratively reweighted lasso estimator and implement the global linear mean-variance model from the associated 2026 Statistics in Medicine article <doi:10.1002/sim.70632>. Under the assumptions in that paper, the estimator matches the homoscedastic baseline in population predictive quasi-risk when variance is constant and improves on it when the variance depends on covariates. The grouping-based nonlinear prediction extension from Section 3 is available in the development version on GitHub.

This package performs an analysis of time-to-event clinical trial data using various "win time" methods, including ewt', ewtr', rmt', ewtp', rewtp', ewtpr', rewtpr', max', wtr', rwtr', pwt', and rpwt'. These methods are used to calculate and compare treatment effects on ordered composite endpoints. The package handles event times, event indicators, and treatment arm indicators and supports calculations on observed and resampled data. Detailed explanations of each method and usage examples are provided in "Use of win time for ordered composite endpoints in clinical trials," by Troendle et al. (2024)<doi:10.1002/sim.10045>. For more information, see the package documentation or the vignette titled "Introduction to wintime.".

This package provides functions to identify Homozygous-by-Descent (HBD) segments associated with runs of homozygosity (ROH) and to estimate individual autozygosity (or inbreeding coefficient). HBD segments and autozygosity are assigned to multiple HBD classes with a model-based approach relying on a mixture of exponential distributions. The rate of the exponential distribution is distinct for each HBD class and defines the expected length of the HBD segments. This rate is called the "rate of coancestry change". The HBD classes are therefore related to the age of the segments (longer segments and smaller rates for recent autozygosity / recent common ancestor). The functions allow to estimate the parameters of the model (rates of the exponential distributions called also rates of coancestry change; mixing proportions related to the inbreeding rate per layer or generation), to estimate global and local autozygosity probabilities and to identify HBD segments with the Viterbi decoding. Functions also allow to compute identity-by-descent (IBD) between pairs of haplotypes, to estimate kinship between pairs of individuals and to predict inbreeding in the future progeny of a genotyped couple. The current model is fully described in Druet and Gautier (2022) <doi:10.1016/j.tpb.2022.03.001>. The model and its properties were originally presented in Druet and Gautier (2017) <doi:10.1111/mec.14324>. Extension to IBD and kinship analyses is described in Forneris et al. (2025) <doi:10.1111/1755-0998.14068>.

Time-varying coefficient models for interval censored and right censored survival data including 1) Bayesian Cox model with time-independent, time-varying or dynamic coefficients for right censored and interval censored data studied by Sinha et al. (1999) <doi:10.1111/j.0006-341X.1999.00585.x> and Wang et al. (2013) <doi:10.1007/s10985-013-9246-8>, 2) Spline based time-varying coefficient Cox model for right censored data proposed by Perperoglou et al. (2006) <doi:10.1016/j.cmpb.2005.11.006>, and 3) Transformation model with time-varying coefficients for right censored data using estimating equations proposed by Peng and Huang (2007) <doi:10.1093/biomet/asm058>.

Provide an optimal histogram, in the sense of probability density estimation and features detection, by means of multiscale variational inference. In other words, the resulting histogram servers as an optimal density estimator, and meanwhile recovers the features, such as increases or modes, with both false positive and false negative controls. Moreover, it provides a parsimonious representation in terms of the number of blocks, which simplifies data interpretation. The only assumption for the method is that data points are independent and identically distributed, so it applies to fairly general situations, including continuous distributions, discrete distributions, and mixtures of both. For details see Li, Munk, Sieling and Walther (2016) <arXiv:1612.07216>.

Using mixed effects models to analyse longitudinal gene expression can highlight differences between sample groups over time. The most widely used differential gene expression tools are unable to fit linear mixed effect models, and are less optimal for analysing longitudinal data. This package provides negative binomial and Gaussian mixed effects models to fit gene expression and other biological data across repeated samples. This is particularly useful for investigating changes in RNA-Sequencing gene expression between groups of individuals over time, as described in: Rivellese, F., Surace, A. E., Goldmann, K., Sciacca, E., Cubuk, C., Giorli, G., ... Lewis, M. J., & Pitzalis, C. (2022) Nature medicine <doi:10.1038/s41591-022-01789-0>.

Performance measures and scores for statistical classification such as accuracy, sensitivity, specificity, recall, similarity coefficients, AUC, GINI index, Brier score and many more. Calculation of optimal cut-offs and decision stumps (Iba and Langley (1991), <doi:10.1016/B978-1-55860-247-2.50035-8>) for all implemented performance measures. Hosmer-Lemeshow goodness of fit tests (Lemeshow and Hosmer (1982), <doi:10.1093/oxfordjournals.aje.a113284>; Hosmer et al (1997), <doi:10.1002/(SICI)1097-0258(19970515)16:9%3C965::AID-SIM509%3E3.0.CO;2-O>). Statistical and epidemiological risk measures such as relative risk, odds ratio, number needed to treat (Porta (2014), <doi:10.1093%2Facref%2F9780199976720.001.0001>).