Elsevier

Journal of Critical Care

Volume 43, February 2018, Pages 401-405
Journal of Critical Care

Critical Care and Personalized or Precision Medicine: Who needs whom?

https://doi.org/10.1016/j.jcrc.2017.11.026Get rights and content

Abstract

The current paradigm of modern healthcare is a reactive response to patient symptoms, subsequent diagnosis and corresponding treatment of the specific disease(s). This approach is predicated on methodologies first espoused by the Cnidean School of Medicine approximately 2500 years ago. More recently escalating healthcare costs and relatively poor disease treatment outcomes have fermented a rethink in how we carry out medical practices. This has led to the emergence of “P-Medicine” in the form of Personalized and Precision Medicine. The terms are used interchangeably, but in fact there are significant differences in the way they are implemented. The former relies on an “N-of-1” model whereas the latter uses a “1-in-N” model. Personalized Medicine is still in a fledgling and evolutionary phase and there has been much debate over its current status and future prospects. A confounding factor has been the sudden development of Precision Medicine, which has currently captured the imagination of policymakers responsible for modern healthcare systems. There is some confusion over the terms Personalized versus Precision Medicine. Here we attempt to define the key differences and working definitions of each P-Medicine approach, as well as a taxonomic relationship tree. Finally, we discuss the impact of Personalized and Precision Medicine on the practice of Critical Care Medicine (CCM). Practitioners of CCM have been participating in Personalized Medicine unknowingly as it takes the protocols of sepsis, mechanical ventilation, and daily awakening trials and applies it to each individual patient. However, the immediate next step for CCM should be an active development of Precision Medicine. This developmental process should break down the silos of modern medicine and create a multidisciplinary approach between clinicians and basic/translational scientists.

Introduction

Over the past several decades Critical Care Medicine (CCM) has been awash in data acquisition and analysis. Many leading CCM centers have built database repositories where every vital sign, clinical finding and patient note is continuously recorded and stored for real-time and future analyses [1]. With the current burgeoning computing power and the emergence of “big data analytics” many subtle trends are beginning to emerge that have allowed for more accurate and timely diagnosis of many different disease states. These data allow for a better understanding of disease onset and progression and thus facilitate earlier and more efficacious treatment. At the same time protocols and/or algorithms have been developed to tackle everything from acute coronary syndrome to sepsis [2], [3]. These algorithms have been used to simplify and standardize the care that patients receive. This standardization of care, has certainly improved outcomes, but at what cost?

Hippocrates (born circa 460 BCE), regarded as the “Father” of modern medicine, believed that disease was a product of environmental forces, diet and lifestyle habits, and that treatment should focus on patient care (prevention) and prognosis (prediction). He argued that the human body functioned as one unified organism and should be treated as a coherent entity. In the diagnosis of disease, he believed that both subjective reporting by patients as well as objective assessment of disease symptoms must be considered. He helped found the Coan School of Medicine and should more accurately be described as the “Father” of Personalized Medicine, with an emphasis on the prevention, prediction, diagnosis and treatment of disease as it pertains to the individual patient [4], [5] (see Fig. 1). This practice has been dramatically eroded over time by the “protocolization” of medicine.

The current modus operandi of modern medicine is predicated on the Cniderean School of Medicine (see Fig. 1) and consists of; i) determination of an individual's symptoms and an associated diagnosis; ii) comparison to a statistically similar and relevant patient population dataset or database; iii) therapeutic treatment and subsequent response to that specific intervention. There is also a focus on a specific disease indication as it pertains to compartmentalized tissue and/or organs involving a highly specialized clinician. The current health-care system tends to be reactive, providing treatment post-onset of the disease, with limited attempts at prevention and prediction. All this reliance on the comparative analysis of an individual compared to a defined population tends to neglect and disregard human individuality, complexity and variability [6].

More recently there has been a backlash to such a medical system, as providers and patients have started to demand more personalized care. The clamor for change has led to the emergent growth of “P-Medicine”. The P-Medicine list of endeavors includes Personalized, Precision, Preventive, Predictive, Pharmacotherapeutic and Patient Participatory Medicine [6]. Current conventional medicine seeks to treat disease post-onset based on the population model described above. In contrast P-Medicine attempts in part, to identify problems pre-onset of the disease and prior to expression of specific clinical pathologies somewhat reminiscent, of the Coan philosophy of medicine espoused by Hippocrates (see Fig. 1). In this paper, we discuss the principal differences between Personalized versus Precision Medicine and how this is relevant to the current and future practice of CCM.

Section snippets

Personalized versus Precision Medicine

As with any new and emerging field of endeavor, clear definitions are often a work in progress as terminology evolves and/or disappears. In the case of Personalized and Precision Medicine it is complicated by the fact that these terms are often used interchangeably as umbrella descriptors. Hence, the terms Personalized and/or Precision Medicine and how they are implemented and practiced have broad and confusing interpretations as well as consequences.

Current perspectives

The oncology community consisting of physicians and researchers has readily embraced elements of both Personalized and Precision medicine. In contrast CCM has found itself moving toward protocol driven care since Rivers and colleagues first published their findings of goal directed therapy in sepsis [25]. They reported for any patient with septic shock that early goal directed therapy uniformly improved the rate of survival. The measures that were outlined did not consider the gender,

Conclusions

Personalized Medicine is an N-of-1 model where each patient is considered to be the only patient being treated. While this model is directed to the patient in front of the intensivist this model does not allow for research or improvements of medicine as a whole. The Precision Medicine model of 1-in-N allows for the more traditional western medicine approach of doing research on groups and sub-groups and treating the patient's specific subgroup. In the examples above it is clear the personalized

Conflicts of interest

Neither author has any conflicts of interest.

Financial disclosure

None for either author.

Acknowledgements

We would like to thank Mr. Andrew Jackson (flaircreativedesign.com) for his help in originally creating and modifying Fig. 1.

Shihab Sugeir is an anesthesiologist and intensivist at University of Southern California Keck School of Medicine. He currently is the co-director of the Post Anesthesia Care Unit and division chief of the Perioperative Home. He completed his fellowship training, in Critical Care Medicine, at Mayo Clinic in Rochester, MN, USA. Correspondence can be addressed to him at [email protected].

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    Shihab Sugeir is an anesthesiologist and intensivist at University of Southern California Keck School of Medicine. He currently is the co-director of the Post Anesthesia Care Unit and division chief of the Perioperative Home. He completed his fellowship training, in Critical Care Medicine, at Mayo Clinic in Rochester, MN, USA. Correspondence can be addressed to him at [email protected].

    Stephen Naylor is the current Founder and CEO of ReNeuroGen LLC, a virtual pharmaceutical company developing precision medicine therapies for the treatment of stroke and other neuroinflammatory and neurodegenerative diseases. In addition, he is the Founder, Chairman and CEO of MaiHealth Inc., a systems/network biology level diagnostics company in the health/wellness and precision medicine sector. He was also the Founder, CEO and Chairman of Predictive Physiology & Medicine (PPM) Inc., one of the world's first personalized medicine companies. He serves also as an Advisory Board Member of CureHunter Inc. a computational biology drug discovery company, and as a business adviser to the not-for-profit Cures Within Reach. In the past, he has held professorial chairs in Biochemistry & Molecular Biology; Pharmacology; Clinical Pharmacology and Biomedical Engineering, all at Mayo Clinic in Rochester, MN, USA. He holds a PhD from the University of Cambridge (UK), and undertook a NIH funded fellowship at MIT located in the “other” Cambridge, USA.

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