Guest Blog
by Ralph Snyderman, M.D., James B. Duke Professor of Medicine, Chancellor Emeritus, Duke University

Ralph Snyderman, M.D.

A Chancellor’s Tale:  Transforming Academic Medicine is a personal and intimate story of my 15-year journey as Duke University’s Chancellor for Health Affairs during a time of major upheaval in medicine. The story, I hope, will help demonstrate the importance of planning, leadership and organizational change to the advancement of the personalized medicine paradigm.

My experience as a scientist and a physician prior to assuming my role as chancellor did little to prepare me to deal with a highly complex and entrenched institution that, unbeknownst to itself, was in need of disruptive change. The story describes the path the institution and I took during my tenure as chancellor, during which time the Duke University Medical Center became known for innovations in medicine and the conception of personalized health care.

As CEO of the Duke University Health System, I saw that despite our delivering outstanding, state-of-the-art care, treatments were generally directed towards the reversal of episodes of late-stage disease.  By 2000, anticipating the power of genomics and associated advances in technology, my colleagues and I began to envision an entirely new approach to care.  Rather than being reactive to disease, health care could be proactive, predictive, preventive and personalized.  As health and disease are a consequence of one’s genetics and environmental exposures over time, the availability of technologies to quantify health risks, track disease progression and identify specific disease mechanisms could be a game-changer for how care is delivered.  Rather than starting with a disease manifestation and working back, clinicians could, in conjunction with their patient, anticipate disease risks and work to mitigate them and to treat them precisely when needed.  As a consequence of this thinking, my colleagues and I conceived of an entirely new approach to health care and in doing so, laid the foundation for personalized health care.

A Chancellor’s Tale tells the story of the major transformation of Duke’s academic enterprise along with the concepts that resulted in the creation of care delivery models for personalized, proactive, patient-driven care. The book describes the difficulties of making change in a complex academic institution including what worked, what went wrong and lessons learned.  My hope is that the personalized medicine community will find the stories interesting and my learning experiences useful.

The book is available for purchase at https://www.dukeupress.edu/a-chancellors-tale.

Special offer: Use coupon code E16SNYDR to save 30 percent on the hardcover edition when you order from dukeupress.edu.

Guest Blog
by Elaine Lyon, Ph.D., Medical Director of Genetics, Genomics and Pharmacogenomics at ARUP Laboratories, Professor of Pathology at the University of Utah School of Medicine, Co-chair of the FEND task force, Senior author of the FEND publication

Elaine Lyon, Ph.D.

Recent advances in genomic medicine continue to provide many new opportunities to improve our modern health care system. However, before we can truly realize the full promise of precision medicine, we need a more practical and patient-centered approach for evaluating clinical usefulness for these types of molecular testing procedures. Current models for clinical utility evaluation clearly fall short of ensuring best care and usefulness for the patient, their family, their provider, and the health care system. While personalized medicine is driving health care progress today, this restricted definition of clinical utility is putting on the brakes and impeding progress.

Since the new molecular pathology Current Procedural Terminology (CPT) codes were implemented, the roles of clinical validity and clinical utility have been the subject of intense discussion. Many stakeholders have adopted very narrow definitions that do not address all the important applications, including diagnosis, prognosis, risk assessment, prediction of future disease, as well as monitoring and selection of therapies.

The ongoing shift of payer expectations from a “reasonable and necessary” to a “demonstrable clinical utility” requirement can be a difficult and unrealistic expectation for laboratories. Since the new requirement was created with therapeutic products in mind, applying the same standards to a test that is designed to establish a diagnosis for an inherited condition is difficult. Even if the test performs flawlessly, the patient may never be “cured” or ‘’treated;” symptoms may only be managed.   In addition, many of these procedures are for diseases so rare that a statistically valid study would be almost impossible, or would at least take many years to complete. Ultimately, we need to capture evidence for the clinical utility of these procedures outside of a traditional randomized control trial setting. To achieve maximum benefit, we need to recognize that any individual test result is an intermediate outcome that relies on proper clinical interpretation and utilization in context for that specific patient.

For example, if a patient with breast cancer tests negative for specific BRCA 1/2 mutations, the physician may move forward with specific drug therapy treatment based on this information; however, the very same test may be used for someone who doesn’t have breast cancer but is being tested because there is a strong family history of breast cancer. In this case, the test is used as a screening tool before the onset of disease. It really depends on how the physician uses the information.

I currently co-chair the Association for Molecular Pathology (AMP) Framework for the Evidence Needed to Demonstrate (FEND) Clinical Utility Task Force, which was formed two years ago to address these specific challenges. The task force seeks to represent the views of the more than 2,300 AMP members, who are fully embedded in the various disciplines of molecular diagnostics, including infectious diseases, inherited conditions and oncology. AMP’s members include individuals from academic and community medical centers, government and industry, including pathologist and doctoral scientist laboratory directors, basic and translational scientists, technologists and trainees.

The FEND task force recently authored a new report published in The Journal of Molecular Diagnostics that establishes a new standard for clinical utility of molecular diagnostics for inherited diseases and cancer. One of our early goals was to have a peer-reviewed publication that could help start the next wave of discussions with all key stakeholders. In the report, we recommend a broad, patient-centered definition that takes into account the different ways that a test might be used, with an understanding that the test results may indicate follow-on activities that are not as simple as merely determining which drug to prescribe, or at what dose. Our inclusive approach utilizes a modified ACCE model and emphasizes that a clinical test result’s utility depends on the context in which it is used to classify a patient’s disease or disorder and/or guide management. We were very careful to make recommendations that can be extended to additional applications of molecular testing.

We believe our recommendations provide a reasonable and feasible path forward that puts patients and their families at the center of evaluating clinical utility for molecular testing procedures. We look forward to continued stakeholder engagement to further advance clinical genomics so that we can begin to realize the full promise of personalized medicine.

To read the full-text, free report, please visit http://dx.doi.org/10.1016/j.jmoldx.2016.05.007.