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THE DIGITAL PATIENT

C. Donald Combs

School of Health Professions, Eastern Virginia Medical School, Norfolk, VA, USA

Whatever we do together is pure invention,
The maps they gave us were out of date by years.

-Adrienne Rich, 21 Love Poems

"Men's courses will foreshadow certain ends, to which, if persevered in, they must lead," said
Scrooge."But if the courses be departed from, the ends will change."

-Charles Dickens, A Christmas Carol

It is, perhaps, odd to begin a book about a highly technical subject, the Digital Patient, with quotations from a poem and a book that, in very different ways, confront the vagaries of relationships. Then again, perhaps it is not so odd after all. Rich identifies the reality that relationships change and head in unexpected directions and that, often, what we thought was settled turns out to be in flux. Dickens describes the inevitable intertwining of past, present, and future in a hopeful homily. Imagine if we could all, without the ghosts, have the opportunity to revisit our past, understand clearly how it affects the present, and realize that the future can be changed into a more rounded, healthier human experience. In its essence, that is what the Digital Patient entails-the development of an evolving foundation for a better future in terms of personal and population health, in the validity of biological and social research, and in the development of more effective drugs and devices.

Dickens' story is a useful metaphor because it invokes the passage of time and describes that passage within a social context. Incorporating those two factors, time and social context, into the discussion of the Digital Patient foreshadows the emergence of an infinite array of applications that will advance our understanding of health and the factors affecting its realization. This introductory chapter provides some historical context for the concept of a Digital Patient, refines the definition to reflect explicitly the impact of the emerging fields of systems biology and computational physiology, and provides a rationale for the chapters that follow. The chapter draws heavily from the writings of Vanessa Díaz-Zuccarini, Peter Hunter, Robert Hester, Leroy Hood, Richard Satava, Peter M. A. Sloot, and other chapter authors. It draws as well from the research conducted by hundreds of international researchers who address topics important to the Digital Patient as diverse as Big Data, the human physiome, systems biology, human behavior, multiscale modeling and simulation, ontologies in healthcare, and Bayesian analysis.

HEALTH, THE GOAL

The most widely accepted definition of health is the one developed by the World Health Organization: Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity [1]. The definition applies to individuals and to populations. From a societal perspective, achieving the goal of health, both individually and as a whole, is why we fund (through both public and private sources) research and development efforts in the domains related to the Digital Patient.

PERSONALIZED MEDICINE

Historically, understanding in detail and with certainty what is going on within the human body has been an elusive quest. Partial glimpses and general understanding are the best we have been able to do with the data we have at our disposal and within the limitations of population-normed theories of what the data mean for the diagnosis and treatment of individuals. In the not-too-distant future, however, that will change as the Digital Patient is developed. The capacity to measure one's personal physiological and social metrics, compare those metrics with the metrics of millions of other humans, personalize needed therapeutic interventions, and measure the resulting changes will realize the vision of personalized medicine. The capacity to aggregate and integrate data from millions of individuals will provide a means to improve health across populations with differing cultures and behaviors.

President Barack Obama stated in the 2015 State of the Union speech that his administration wants to increase the use of personalized genetic information to help treat diseases such as cancer and diabetes. He urged Congress to boost research funding to support new investments in precision medicine. Obama wants "the country that eliminated polio and mapped the human genome to lead a new era of medicine-one that delivers the right treatment at the right time" [2, 3].

He will seek hundreds of millions of dollars for a new initiative to develop medical treatments tailored to genetic and other characteristics of individual patients. "Most medical treatments have been designed for the average patient," said Jo Handelsman, associate director of the White House Office of Science and Technology Policy. "In too many cases, this one-size-fits-all approach is not effective." Dr. Ralph Snyderman, a former chancellor for health affairs at Duke University, often described as the father of personalized medicine, said he was excited by the president's initiative. "Personalized medicine has the potential to transform our healthcare system, which consumes almost $3 trillion a year, 80% of it for preventable diseases," said Dr. Snyderman [3].

THE BEST OUTCOMES

A patient is a person who is receiving healthcare. Healthcare involves surveillance, diagnosis, treatment, monitoring, and quality assessment. The goal of healthcare is, of course, a healthy outcome. Several analytic frameworks for assessing quality have guided initiatives in the public and private sectors to develop measures of the outcomes of healthcare. One of the most influential is the framework put forth by the Institute of Medicine (IOM), which includes the following goals for the healthcare system [4]:

• Safety, avoiding harm to patients from the care that is intended to help them.
• Effectiveness, providing services based on scientific knowledge to all who could benefit and refraining from providing services to those not likely to benefit (avoiding underuse and misuse, respectively).
• Patient-centered, providing care that is respectful of and responsive to individual patient preferences, needs, and values and ensuring that patient values guide all clinical decisions.
• Timeliness, reducing waits and sometimes harmful delays for both those who receive and those who give care.
• Efficiency, avoiding waste, including waste of equipment, supplies, ideas, and energy.
• Equity, providing care that does not vary in quality because of personal characteristics such as gender, ethnicity, geographic location, and socioeconomic status.

Having the goal of improved healthcare outcomes in mind helps to frame the importance of the Digital Patient: it is among the most powerful technological tools that we can develop and deploy to improve health outcomes. The Digital Patient is not a panacea; it will become, however, an essential component of the twenty-first-century healthcare toolkit.

THE EMERGENCE OF THE DIGITAL PATIENT

The Digital Patient's origins are recent, tied as they are to computer and imaging technologies developed during past 40 years. Although some of the modeling related to the human physiome dates back to the early 1980s and the emergence of computers as a significant factor in biomedical research, the clearest point of origin for the Digital Patient is the US Library of Medicine's Visible Human Project (VHP).

The Visible Human

The VHP has now celebrated the twentieth anniversary of the completion of the male (1993) and female (1994) image collections [5]. The data has been used broadly and remains a primary resource for research in the areas of human modeling and simulation of structures. The need for the VHP was predicted by the National Library of Medicine's (NLM) 1986 Long-Range Plan to include applications in education, training, modeling, simulation, morphometrics, information interfaces, reference standards, and entertainment [6].

The VHP (described more fully in Chapter 5) has contributed significantly to the education and training of both healthcare professionals and the general public. The data have been used extensively in atlases of both cross-sections and three-dimensional images of the human anatomy. The segmented image data has been the foundation for models used for 3D printing and virtual and augmented reality surgical simulators. Yet, further dynamic tissue modeling enhancements are needed to bring the Visible Human's cadaveric anatomical images to life.

Dead humans, such as the cadavers used in the VHP, are obviously not the same as living humans. They are, however, very useful models of human anatomy, both diseased and healthy. The data derived from analysis of human anatomic structures is an important component of the Digital Patient. That said, the pressing challenge is to build accurate human simulations, comprising many interacting models, capable of representing living humans moving through time.

THE HUMAN PHYSIOME

There are several international collaborative efforts directed toward the analysis of the human physiome. Two of those most inclusive efforts are described here. The International...