A range of regularization approaches have been proposed in the data sciences to overcome overfitting, to exploit sparsity or to improve prediction. Using a broad definition of regularization, namely controlling model complexity by adding information in order to solve ill-posed problems or to prevent overfitting, we review a range of approaches within this framework including penalization, early stopping, ensembling and model averaging. Aspects of their practical implementation are discussed including available R-packages and examples are provided. To assess the extent to which these approaches are used in medicine, we conducted a review of three general medical journals. It revealed that regularization approaches are rarely applied in practical clinical applications, with the exception of random effects models. Hence, we suggest a more frequent use of regularization approaches in medical research. In situations where also other approaches work well, the only downside of the regularization approaches is increased complexity in the conduct of the analyses which can pose challenges in terms of computational resources and expertise on the side of the data analyst. In our view, both can and should be overcome by investments in appropriate computing facilities and educational resources.

Aims: Artificial intelligence (AI) and machine learning (ML) promise vast advances in medicine. The current state of AI/ML applications in cardiovascular medicine is largely unknown. This systematic review aims to close this gap and provides recommendations for future applications. Methods and results: Pubmed and EMBASE were searched for applied publications using AI/ML approaches in cardiovascular medicine without limitations regarding study design or study population. The PRISMA statement was followed in this review. A total of 215 studies were identified and included in the final analysis. The majority (87%) of methods applied belong to the context of supervised learning. Within this group, tree-based methods were most commonly used, followed by network and regression analyses as well as boosting approaches. Concerning the areas of application, the most common disease context was coronary artery disease followed by heart failure and heart rhythm disorders. Often, different input types such as electronic health records and images were combined in one AI/ML application. Only a minority of publications investigated reproducibility and generalizability or provided a clinical trial registration. Conclusions: A major finding is that methodology may overlap even with similar data. Since we observed marked variation in quality, reporting of the evaluation and transparency of data and methods urgently need to be improved.

To date, there is a lack of satisfactory inferential techniques for the analysis of multivariate data in factorial designs, when only minimal assumptions on the data can be made. Presently available methods are limited to very particular study designs or assume either multivariate normality or equal covariance matrices across groups, or they do not allow for an assessment of the interaction effects across within-subjects and between-subjects variables. We propose and methodologically validate a parametric bootstrap approach that does not suffer from any of the above limitations, and thus provides a rather general and comprehensive methodological route to inference for multivariate and repeated measures data. As an example application, we consider data from two different Alzheimer’s disease (AD) examination modalities that may be used for precise and early diagnosis, namely, single-photon emission computed tomography (SPECT) and electroencephalogram (EEG). These data violate the assumptions of classical multivariate methods, and indeed classical methods would not have yielded the same conclusions with regards to some of the factors involved.