Heterogeneity, Bayesian thinking, and phenotyping in critical care: A primer

Purpose To familiarize clinicians with the emerging concepts in critical care research of Bayesian thinking and personalized medicine through phenotyping and explain their clinical relevance by highlighting how they address the issues of frequent negative trials and heterogeneity of treatment effect.Summary The past decades have seen many negative (effect-neutral) critical care trials of promising interventions, culminating in calls to improve the field's research through adopting Bayesian thinking and increasing personalization of critical care medicine through phenotyping. Bayesian analyses add interpretive power for clinicians as they summarize treatment effects based on probabilities of benefit or harm, contrasting with conventional frequentist statistics that either affirm or reject a null hypothesis. Critical care trials are beginning to include prospective Bayesian analyses, and many trials have undergone reanalysis with Bayesian methods. Phenotyping seeks to identify treatable traits to target interventions to patients expected to derive benefit. Phenotyping and subphenotyping have gained prominence in the most syndromic and heterogenous critical care disease states, acute respiratory distress syndrome and sepsis. Grouping of patients has been informative across a spectrum of clinically observable physiological parameters, biomarkers, and genomic data. Bayesian thinking and phenotyping are emerging as elements of adaptive clinical trials and predictive enrichment, paving the way for a new era of high-quality evidence. These concepts share a common goal, sifting through the noise of heterogeneity in critical care to increase the value of existing and future research.Conclusion The future of critical care medicine will inevitably involve modification of statistical methods through Bayesian analyses and targeted therapeutics via phenotyping. Clinicians must be familiar with these systems that support recommendations to improve decision-making in the gray areas of critical care practice.