Personalized Critical Care Medicine: How Far Away Are We?

Abstract

Personalized medicine has typically referred to the use of genomics in clinical care. However, the concept more broadly refers to recognizing the heterogeneity of each individual patient, particularly their unique risk factors for developing disease or having poor outcomes, and using this to inform treatment decisions. Pharmacogenomics was perhaps the first major clinical application that came out of the Human Genome Project, but its translation to the critical care arena has been limited by numerous factors. Biomarkers have been widely studied in critical illnesses such as sepsis and acute respiratory distress syndrome in an attempt to aid in accurate diagnostic classification, to predict outcomes, and to assess response to therapy. Clinical use of such biomarkers has remained limited, but multi-biomarker panels have attempted to better reflect the complex physiology of critical illness, and to assist in design and recruitment for clinical trials. Genetic association and gene expression studies have been aimed at classifying risk for and severity in disease, as well as in predicting outcomes. While our understanding of the pathogenesis of critical illness has progressed significantly, the clinical utility of genetic markers remains limited. Novel methods are reaching closer to clinically applicable platforms, both for use in clinical trials and in direct patient care. Although we are not yet living in an era of personalized and precise medical care in the intensive care unit, the future is promising.

The coming era of precision medicine for intensive care

“…For example, a study comparing the immunostimulating drug granulocyte–macrophage colony-stimulating factor (GM-CSF) with placebo is currently ongoing, enrolling only patients know to be immunodepressed based on their human leukocyte antigen (HLA)-DR level (ClinicalTrials.gov NCT02361528). Pharmacogenomics is widely used in some cancer therapies, but has not yet been widely studied in the ICU, partly because genomic testing is not yet available sufficiently rapidly for use in the acute critical illness situation [ 19 ]. However, genetic variations and polymorphisms have been shown to influence the response and adverse effects of several drugs relevant to the critically ill population, including morphine, dexmedetomidine, vasopressin, and catecholamines [ 20 ].…”

Benchmarking analysis of deleterious SNP prediction tools on CYP2D6 enzyme

“…A detailed description of each prediction is available on Table S7 T A B L E 3 Sensitivity (SEN), specificity (SPC), accuracy (ACC) and approximated diagnostic odds ratio (DOR) of the twenty predictive tools of SNPs as rare mutations; and those could be important for developing personalized medicine. To this end, instead of the traditional "one-size-fits-all" approach to drug therapy, the application of targeted drug therapy could allow a more personalized approach, thus minimizing the occurrence of therapeutic failures or adverse effects (Ahasic & Christiani, 2015;Hertz & McLeod, 2016). There is a vast range of tools for predicting the functional effect of missense SNPs based on different methodologies.…”

Benchmarking analysis of deleterious SNP prediction tools on CYP2D6 enzyme

“…This information is of great importance for pharmacogenomics to determine responses to drug action in relation to the genetic variations of individuals. To this end, instead of the traditional "one size fits all" approach to drug therapy, the application of targeted drug therapy could allow a more personalized approach, thus minimizing the occurrence of therapeutic failures or adverse effects (Ahasic & Christiani, 2015;Hertz & McLeod, 2016).…”