Box–Cox–type Transformations for Linear and Logistic Models with Random Effects.

Random effect models have become a mainstream statistical technique over the last decades; and the same can be said for response transformation models such as the Box-Cox transformation. The latter ensures that the assumptions of normality and of homoscedasticity of the response distribution are fulfilled, which are essential conditions for the use of a linear model or a linear mixed model. However, methodology for response transformation and simultaneous inclusion of random effects has been developed and implemented only scarcely, and is so far restricted to Gaussian random effects. The first aim of this thesis is to develop such methodology, thereby not requiring parametric assumptions on the distribution of the random effects. This is achieved by extending the “Nonparametric Maximum Likelihood” towards a “Nonparametric Profile Maximum Likelihood” (NPPML) technique. The implemented techniques allow to deal with overdispersion as well as two-level data scenarios in general linear models. The second part of this thesis considers the transformation of mixed-effects logistic models, with the aim of improving model fit. In binary data, link functions other than the logit can be used to connect predictors with the response. The Box-Cox transformation is used in mixed–effects binary regression models as an alternative link function for linearization purposes. The NPPML approach is used similarly as before, with some adjustments. The proposed approach is implemented in the R package boxcoxmix. Simulation studies and applications on real data are carried out to study the performance of this approach

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population